Ovarian development in mice bearing homozygous or heterozygous null mutations in zona pellucida glycoprotein gene mZP3.
The plasma membrane of all mammalian eggs is surrounded by a thick extracellular coat, the zona pellucida (ZP), whose paramount function is to regulate species-specific fertilization. The mouse egg ZP is composed of only three glycoproteins, mZP1-3, that are synthesized and secreted exclusively by oocytes during their 2-3 week growth phase. Disruption of the mZP3 gene by targeted mutagenesis in embryonic stem (ES) cells yields mice heterozygous (mZP3 +/-) or homozygous (mZP3-/-) for the null mutation. As expected, male mice bearing the null mutation are indistinguishable from wild-type males with respect to viability and fertility. Female mZP3 +/- mice are as fertile as wild-type animals, but their eggs have a thin ZP (approximately 2.7 microns thick) as compared to the ZP (approximately 6.2 microns thick) of eggs from wild-type animals. On the other hand, female mZP3-/- mice are infertile and their eggs lack a ZP. The infertility apparently is due to the lack of a sufficient number of eggs in oviducts of superovulated mZP3-/- females. Light micrographs reveal that development of ovarian follicles is often retarded in mZP3-/- mice as compared to wild-type animals. This is manifested as reduced ovarian weights, reduced numbers of Graafian follicles, and reduced numbers of fully-grown oocytes in mZP3-/- females. It seems likely that the pleiotropic effects of the homozygous null mutation on ovarian development may be due, at least in part, to disruption of intercellular communication between growing oocytes and their surrounding follicle cells.
Wassarman
P M
PM
Department of Cell Biology and Anatomy, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
Liu
C
C
Chen
J
J
Qi
H
H
Litscher
E S
ES
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D002874:Chromosome Mapping; D004527:Egg Proteins / Q000032:analysis* / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D016296:Mutagenesis; D010053:Ovary / Q000254:growth & development*; D010641:Phenotype; D011956:Receptors, Cell Surface; D013084:Sperm-Ovum Interactions; D015044:Zona Pellucida / Q000737:chemistry / Q000502:physiology*; D000072216:Zona Pellucida Glycoproteins
D004527:Egg Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000072216:Zona Pellucida Glycoproteins